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Biomedical subjects

J Keen

Publications and source records attributed to J Keen.

At least 55 records · Page 3Linked to original sources

Evaluation of diffuse technologies: the case of digital imaging networks.

There have been significant developments in recent years in the methodologies and methods for the evaluation of a wide range of health technologies. There remain, though, many technologies which are difficult to evaluate. Often the difficulty stems from the complexity of the technologies themselves, which are in effect hybrids, comprising combinations of several distinct elements. In this paper these are termed 'diffuse' technologies, because the different elements exert different costs and effects, often across several different services. Computer networks are one, increasingly important, example of such technologies in health care. While it is possible to evaluate individual elements of such technologies, it is not clear how to evaluate the technology as a whole, where the whole may be greater (or less) than the sum of the parts. The paper outlines a seven-stage framework for the evaluation of diffuse technologies. The general principles of evaluation are illustrated using the example of picture archiving and communication systems (PACS), which are computer systems designed to capture, store and distribute electronic radiological images within a hospital.

Cost-Benefit Analysis↗

Information strategy in the NHS: issues and challenges.

There has been considerable discussion of the nature and scope of information that purchasers and providers must acquire and use in the post-review NHS. Somewhat surprisingly, this has not been complemented by discussion of the potential for computer systems to support information management. This in spite of the publication of the NHS Information Management and Technology Strategy, which seems set to shape the way in which purchasers and providers manage data into the next century, and expenditure on computer systems which will be in the order of hundreds of millions of pounds over the next few years. Discusses some of the key challenges involved in implementing an IT infrastructure across the NHS, and identifies five issues which will substantially determine the success of the strategy.

Computer Systems↗

Explaining variation in radiologists' reporting times.

This paper describes an investigation into the reasons for variation in the time taken by senior radiologists to complete radiological reports. An observational study of the reporting process at one UK hospital was undertaken for a 25 day period. An independent health service researcher observed the radiology reporting process and collected data on a variety of factors including the time taken to produce the report, the number and nature of all images viewed, the experience of the radiologist, and the number of disturbances that occurred. The nature of the variation in reporting time was explored using both simple comparative statistics and more sophisticated multiple regression techniques. Data were collected on 2345 report observations and the median report time was 117 s. This research provides the first empirical evidence for systematic variation in reporting time. The results confirm the importance of certain factors that were expected to explain report time variation. For example, the results indicate that report time tended to be significantly shorter in reporting sessions that were busy, and significantly longer when the radiologist was disturbed during the reporting process or was training juniors during a reporting session. More surprising were the results indicating that there was no significant difference in report time for reports categorized as urgent or "hot" and those categorized as less urgent or "cold", and that report time appeared to vary systematically depending on the day of the week and on the time of day.

Humans↗

A comparison of whole virus and recombinant transmembrane ELISA and immunodiffusion for detection of ovine lentivirus antibodies in Italian sheep flocks.

Sera from two sheep experimentally infected with ovine lentivirus (OLV) and from 186 sheep selected from flocks with known high or low prevalence of infection or on the basis of virological or histopathological examination were simultaneously tested by whole virus (WV) ELISA, recombinant transmembrane (r-TM) ELISA and AGID assay. Antigens for both the WV ELISA and AGID were prepared from an Italian field isolate; recombinant antigen was derived from the N'-terminal region of the transmembrane envelope protein of strain K1514. The WV ELISA detected the highest number of seropositives, followed by the r-TM ELISA and AGID test. The sensitivity and specificity of the r-TM ELISA relative to the WV ELISA were 0.66 and 0.95, respectively. Immunoblot analysis of 14 WV ELISA-positive and r-TM ELISA-negative sera showed that the major core protein was immunodominant on WV antigen. It is concluded that the r-TM ELISA was more sensitive than the AGID test but less sensitive that the WV ELISA, particularly for detecting antibodies in the early stages of infection.

Animals↗

Evidence that the 16 kDa proteolipid (subunit c) of the vacuolar H(+)-ATPase and ductin from gap junctions are the same polypeptide in Drosophila and Manduca: molecular cloning of the Vha16k gene from Drosophila.

The 16 kDa proteolipid (subunit c) of the eukaryotic vacuolar H(+)-ATPase (V-ATPase) is closely related to the ductin polypeptide that forms the connexon channel of gap junctions in the crustacean Nephrops norvegicus. Here we show that the major protein component of Manduca sexta gap junction preparations is a 16 kDa polypeptide whose N-terminal sequence is homologous to ductin and is identical to the deduced sequence of a previously cloned cDNA from Manduca (Dow et al., Gene, 122, 355-360, 1992). We also show that a Drosophila melanogaster cDNA, highly homologous to the Manduca cDNA, can rescue Saccharomyces cerevisiae, defective in V-ATPase function, in which the corresponding yeast gene, VMA3, has been inactivated. Evidence is presented for a single genetic locus (Vha16) in Drosophila, which in adults at least contains a single transcriptional unit. Taken together, the data suggest that in Drosophila and Manduca, the same polypeptide is both the proteolipid subunit c component of the V-ATPase and the ductin component of gap junctions. The intron/exon structure of the Drosophila Vha16 is identical to that of a human Vha16 gene, and is consistent with an ancient duplication of an 8 kDa domain. A pilot study for gene inactivation shows that transposable P-elements can be easily inserted into the Drosophila ductin Vha16 gene. Although without phenotypic consequences, these can serve as a starting point for generation of null alleles.

Amino Acid Sequence↗

LOCALIZATION OF ANGIOTENSIN II RESPONSES IN THE TROUT CARDIOVASCULAR SYSTEM

The renin/angiotensin system (RAS) is a tonic anti-drop regulator of arterial blood pressure in many teleosts. In trout, angiotensin II (ANG II) has no direct constrictor effect on large arteries or veins and the identity of specific cardiovascular pressor effectors is unknown. Potential targets of angiotensin activation were examined in the present experiments using perfused organs and isolated tissues from the rainbow trout Oncorhynchus mykiss. Perfused gill (arches 2 and 3), perfused skeletal muscle-kidney (via the dorsal aorta; PDA) and perfused splanchnic (via the celiacomesenteric; PCM) circulations vasoconstrict in response to salmonid ANG II in a dose-dependent manner. ANG II was significantly (P¾0.05) more potent in the PCM than in the PDA, and both preparations were more responsive than the gills: pD2=8.0±0.20 (10) for PCM; pD2=7.5±0.07 (13) for PDA; pD2=6.9 ±0.21 (8) for gill arch 3; pD2=6.7±0.23 (8) for gill arch 2; mean ± s.e.m. (N), respectively. Salmonid angiotensin I (ANG I) also produced a dose-dependent constriction of the PDA and PCM. Angiotensin converting enzyme (ACE) activated nearly 100 % of ANG I to ANG II in a single pass through the PDA, whereas PCM conversion was estimated to be less than 10 %. Inhibitors of adrenergic constriction partially prevented ANG II responses in the PDA but did not affect PCM responses. ANG II did not affect paced rings of ventricular muscle in the presence of high or low [Ca2+] or epinephrine concentrations, nor did it have any inotropic or chronotropic effects in the in situ perfused heart. Red blood cell swelling was unaffected by ANG II. Similarly, the effects of ANG II on gut, urinary bladder and gall bladder smooth muscle were negligible or non-existent; thus, an increase in splanchnic resistance due to extravascular compression can be discounted. These results indicate that, in trout, the systemic microcirculation is the major cardiovascular effector of angiotensin-mediated pressor responses. In addition, the RAS has little direct effect on non-vascular smooth muscle or the heart. From an evolutionary perspective, the initial site of direct systemic RAS action appears to be the vascular microcirculation.

Journal Article↗

Doctors and resource management: incentives and goodwill.

The increasing pressure on resources available for health care in many countries has led to a re-examination of the way in which resources are allocated and committed. One important and innovative option is for managers and doctors to collaborate formally in decision-making. This paper draws on experience of this approach in the UK National Health Service, in the Resource Management Initiative and suggests that its success or failure depends on the nature and strength of the incentives to the two sides to collaborate.

Decision Making, Organizational↗

Mutations in the human retinal degeneration slow (RDS) gene can cause either retinitis pigmentosa or macular dystrophy.

Mutations in the RDS gene, which encodes the photoreceptor glycoprotein peripherin, have been sought in families with autosomal dominant retinal dystrophies. A cysteine deletion at codon 118/119 is associated with retinitis pigmentosa in one. Three families with similar macular dystrophy have mutations at codon 172, arginine being substituted by tryptophan in two and by glutamine in one. A stop sequence at codon 258 exists in a family with adult vitelliform macular dystrophy. These findings demonstrate that both retinitis pigmentosa and macular dystrophies are caused by mutations in RDS and that the functional significance of certain amino-acids in peripherin-RDS may be different in cones and rods.

Adult↗

Evaluation of an ELISA for detection of ovine progressive pneumonia antibodies using a recombinant transmembrane envelope protein.

An enzyme-linked immunosorbent assay (ELISA) was developed using a recombinant protein corresponding to the N'-terminal hydrophilic region of transmembrane glycoprotein (TM) of ovine lentivirus. This assay reproducibly detected antibodies in sera from 207 of 212 ovine progressive pneumonia (OPP) virus-infected sheep, and the recombinant TM ELISA accurately identified 26% (35 vs. 9) more seropositive samples than did the agar gel immunodiffusion test when applied to 100 sera from an infected flock. This assay also yielded no false-positive results in 14 true negative sera. Results of these experiments were further confirmed by the recombinant TM and recombinant p25 Western blot assay. A single recombinant TM antigen, as the coating antigen in ELISA, can be used successfully for the detection of OPP virus-infected animals and can improve the sensitivity and specificity for OPP diagnosis.

Animals↗

Eosinophil chemotactic peptide sequences in rat alpha-CGRP. Activation of a novel trophic action by neutral endopeptidase 24.11.

Rat alpha- and alpha-CGRP are substrates for endopeptidase 24.11 in vitro. Cleavage of both peptides occurs at several points, including an unusual substrate recognition site to the amino side of ala36. In alpha-CGRP this resulted in the early formation of val32-gly-ser-glu35, a sequence previously reported to be a component of the eosinophil chemotactic factor of anaphylaxis (ECF-A). The biological activity of this peptide fragment was confirmed by bioassay. Chemotactic activity in other hydrolysis fragments of both alpha- and beta-CGRP was observed. Both alpha- and beta-CGRP could thus serve as precursors to different eosinophil chemotactic peptide fragments. A novel function of endopeptidase 24.11 may be to modify rather than to terminate the biological activity of CGRP peptides.

Amino Acid Sequence↗

Endopeptidase-24.11 cleaves a chemotactic factor from alpha-calcitonin gene-related peptide.

The sequence of rat alpha-calcitonin gene-related peptide (CGRP-alpha) contains the tetrapeptide eosinophil granulocyte chemotactic factor Val32-Gly-Ser-Glu35. Peptide fragments formed following hydrolysis of rat CGRP-alpha in vitro by endopeptidase-24.11 were identified. The tetrapeptide fragment was generated following cleavage at a substrate recognition site unusual for this enzyme (-Glu-Ala-). Chemotactic activity of rat CGRP-alpha was increased following hydrolysis. Furthermore, rat CGRP-beta, which lacks the tetrapeptide sequence and is completely devoid of chemotactic activity, displayed low but measurable activity after hydrolysis. Val-Gly-Ser-Glu was identified as the principle fragment with chemotactic activity in rat CGRP-alpha. The results show that the chemotactic activity of the neuropeptide rat CGRP-alpha towards eosinophil polymorphonuclear leukocytes is increased following its hydrolysis in vitro by endopeptidase 24.11 through the formation of a previously identified eosinophil chemotactic tetrapeptide.

Amino Acid Sequence↗

Nursing power and practice in the United Kingdom National Health Service.

Over the last decade the National Health Service (NHS) in the United Kingdom has experienced major organizational change. Successive government initiatives designed to improve local management of hospitals have tended to marginalize nurses. Resource Management, a major initiative, which is the model adopted in the NHS Review for hospital management for the 1990s, appeared initially to offer nurses an opportunity to influence decision-making directly. In practice, nurses' experiences of Resource Management were mixed. This study of the six hospitals which piloted the introduction of Resource Management showed that nurses did not always grasp the opportunity to enhance their power and practice. There was evidence from the study that the introduction of information technology curbed innovations in practice, and removed nurses from patient care delivery.

Decision Making, Organizational↗

Process and structure: resource management and the development of sub-unit organisational structure.

Resource Management (RM) requires hospital units to manage their work in new ways, and the new management processes affect, and are affected by, organisation structure. This paper is concerned with these effects, reporting on the basis of a three-year evaluation of the national RM experiment that was commissioned by the DH. After briefly indicating some of the major characteristics of the RM process, the two main types of unit structures existing in the pilot sites at the beginning of the experiment, unit disciplinary structure and clinical directorates, are analysed. At the end of the experiment, while clinical directorates had become more popular, another variant, clinical grouping, had replaced the unit disciplinary structure. Both types of structure represent a movement towards sub-unit organisation, bringing the work and interests of the service providers and unit managers closer together. Their properties are likewise analysed and their implications, particularly in terms of training and organisational development (OD), are then considered. The paper concludes by considering the causes for these structural changes, which, in the immediate time-scale, appear to owe as much to the NHS Review as to RM.

Decision Making, Organizational↗